Immunology - The immune response to infection/ primary immune deficiencies part 1 Flashcards
Incomplete - excludes basics and material that is mentioned in subsequent lectures
Give two examples of pattern recognition receptor
Toll like receptor
Mannose receptor
expressed cells of innate immune mainly to recognise PAMPs
How is pus formed?
Following phagocytosis, neutrophils die
When they die, they release residual enzymes which causes the liquefication of closely adjacent material
This forms pus
What is opsonisation?
Modification of a pathogen to attract it to a NK or phagocytic cell
Enables phagocytosis
opsonins - antibodies, complement components or acute phase proteins
What role do NK cells play in regulating immunity?
Express inhibitory receptors for self-HLA molecules
Describe the changes that occurs in dendritic cells following phagocytosis
- Upregulate expression of HLA-1
- Migrate to lymph nodes (mediated by CCR7)
- Process non-self antigen and present it to T cells in lymph nodes to prime the adaptive immune response
Recall 2 functions of CD4+ T lymphocytes
Provide help for development of:
- Full B cell response
- Some CD8+ T cell responses
Which type of plasma cell is dependent on CD4+ T cells for activation? Which isn’t
IgG is dependent
IgM is not
Which components of complement comprise the classical pathway?
C1 C2 C4
Which components of complement comprise the mannose binding lectin pathway?
C2 C4
What is the role of the membrane attack complex formed at the end of the complement pathway?
punches holes in the plasma membranes of target cells.
What is the first class of immunoglobulin to be made in the adaptive immune response?
IgM
What is the difference between oxidative and non-oxidative killing?
Oxidative: uses NADPH and hydrochlorous acid
Non-oxidative: uses lysosymes
Which form of HLA is recognised by CD4 cells?
HLA-2
Which form of HLA is recognised by CD8 cells?
HLA-1
Which cytokines induce development of CD4 T cells into Th1 cells?
IL2 and IFN gamma
What is the function of Th1 cells?
produce interferon-gamma, interleukin (IL)-2, and tumour necrosis factor (TNF)-beta, which activate macrophages
Which cytokines induce development of CD4 T cells into Th17 cells?
IL6 and TGF beta
Transforming growth factor beta
What is the function of Th17 cells?
‘Help’ neutrophil recruitment
Which cytokine induces development of CD4 T cells into Treg cells?
TGF beta
Which cytokine induces development of CD4 T cells into follicular T helper cells?
IL6
Which type of T cell produces CD25 and FOXP3?
T reg cells
By what mechanism do CD8 cells effect their cytotoxicity?
Injection of perforin, which enables granzyme entry
OR
Fas ligand expression
Which cytokines are secreted by CD8 T cells?
IFN gamma and TNF alpha
How do CD4 cells activate B cells?
Express CD40 ligand, which interacts with CD40 on immature B cell surface, causing the B cell to differentiate
(remember CD40 is absent in hyper IgM)
Recall the 2 processes that B cells undergo to become mature
- Class switching
- Somatic hypermutation
Which part of an immunoglobulin determines its class?
Heavy chain
in total each Ig has 2 heavy and 2 light chains
Which class of immunoglobin forms a pentamer?
IgM
Which class of immunoglobulin forms a dimer?
IgA
Which portion of an immunoglobulin mediates pathogen identification?
Fab portion
Which portion of an immunoglobulin mediates activation of complement/ NK cells?
Fc portion
Where is complement produced?
Liver
What immune cell releases granzyme and perforin when activated?
cytotoxic T cells
CD8 is specifically a marker of what type of immune cell?
cytotoxic T cell
aka T killer cell
What is the minimum number of Fc receptors on the surface of mast cells that must bind to an antigen to cause mast cell degranulation?
2
Immunoglobin E, IgE, is structurally very similar to IgG. It has two antigen binding sites. Is main role is in the protection against parasites and helminths. IgE uniquely binds to a special type of Fc receptor on the surface of mast cells. This binding is one of the strongest non-covalent bonds found in biological systems. This binding is therefore essentially irreversible. If two IgE molecules on the surface of mast cells recognise antigen and cross-link, then this will lead to mast cell activation and in servere cases, anaphylaxis.
what white cell is most abundant in PB
neutrophil
What serine protease released by neutrophils causes hepatitis and emphysema in patients deficient in alpha-1 antitrypsin?
neutrophil elastase
alpha-1 antitrypsin caused by a defect in what gene and what’s the inheritance
autosomal dominant
SERPINA 1 gene
Which cell surface receptor allows cells of the innate immune system to bind to immunoglobulins?
Fc receptor
The Fc receptor is a cell surface receptor found on most cells of the human immune system. It binds the constant region of antibodies and may lead to cellular activation, phagocytosis, or any other number of intracellular events.
what are the acute phase proteins? where are they made
Acute phase reactants (APR) are inflammation markers that exhibit significant changes in serum concentration during inflammation. These are also important mediators produced in the liver during acute and chronic inflammatory states. Interleukin-6 (IL-6) is the primary cytokine responsible for inducing the production in the liver. IL-1, tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) can also induce the production of acute-phase reactants. Acute phase reactants cause several adverse effects. These include fever, anemia of chronic disease, anorexia, somnolence, lethargy, amyloidosis, and cachexia (fat and muscle loss, anorexia, weakness).
Acute phase reactants can be classified as positive or negative, depending on their serum concentrations during inflammation. Positive acute phase reactants are upregulated, and their concentrations increase during inflammation. Negative acute phase reactants are downregulated, and their concentrations decrease during inflammation. Positive acute phase reactants include procalcitonin, C-reactive protein, ferritin, fibrinogen, hepcidin, and serum amyloid A. Negative acute phase reactants include albumin, prealbumin, transferrin, retinol-binding protein, and antithrombin
distinguish between monoclonal and polyclonal antibodies
Monoclonal antibody = a solution of identical antibodies Polyclonal antibody = a solution of mutliple antibodies with different affinities for the same antigen (or target molecule
distinguish between opsonisation and agglutination
Opsonisation is where, as a result of antibodies binding to the surface of a pathogen, an otherwise undigestable pathogen is allowed to be phagocytosed.
Agglutination, on the other hand, is a process where to enhance phagocytosis, an antibody (such as IgM) may bind to multiple pathogens at once to allow for more effective clearance.
what type of immune cell undergoes class switching & somatic hypermutation
B lymphocyte
may switch from producing IgM to IgA for example
somatic hyper = immune system adapts to new microbes, producing new antibodies (ideally of a high affinity but may not be)
CD3 is a marker of what immune cell
all T cells
define neutralisation
the ability of antibodies/immunoglobulins to block the site(s) on bacteria or viruses that they use to enter their target cell.
define sensitisation
immune response is generated against an antigen after exposure
typically no symptoms the first exposure, usually response on second
CD14 is a marker of what immune cell
Macrophages (or monocytes)
CD8 is a marker of what type of cell
cytotoxic T cell
give a treatment option for type 2 hypersensitivity reactions
plasmapheresis allows blood to be cleared of harmful antibodies in short term
CD19 is a marker of what immune cell
B cell at all stages of maturation
which interleukin induces fever
IL 1
What immune cell would recognise a mutated cell that no longer expresses endogenous peptides and MHC Class 1
NK Cell would do it
NKs are from inane immune system - they doting recognise T or B receptors but they do recognise an absence of MHC o imbalance in cell surface receptors
describe the structure of IgG
monomeric antibody w 2 highly specific antigen binding sites
what blood product is most commonly contaminated by bacteria
platelets
what are complements and where are they made
serine proteases made by the liver
state 7 cells of the innate immune system
NK
MONOCYTES
MACROPHAGES
DENDRITIC
NEUTROPHILS
EOSINO
BASO
give 4 features of the innate cells
identical in everyone
phagocytic capacity
express pattern recognition receptors to detect pathogens
secrete cytokines and chemokines
3 soluble components of innate
complement
acute phase proteins
cytokines and chemokines
why do dendritic cells repent the innate-adaptive transition
they express
cytokines to chemokines to detect inflammation
PRRs to detect pathogens
Fc receptors for Ig
what cells have MHC class 1 or MHC class 2
MHC class 1 (HLA A, B, C) - every cell MHC class 2 (HLA DP, DR, DQ) - antigen presenting cells only
what are T reg cells
subset of lymphocytes that express FOXP3 and CD25
where to T cells under selection? how does this occur
thymus
low affinity and high affinity not selected
intermediate affinity for HLA is selected (10% of original cells)
these cells then have affinity of HLA 1 or 2, becoming CD8 & CD4 T cells respectively
TH1 cells express and secret what
express CD4
secreted IFN gamma and IL2
what s at the alternative complement pathway
PAMP (LPS, tectonic acid) to C3
C3 binds bacterial cell wall components
involves factors B, I, P (properdidin)
what is the major amplification step in the complement cascade
C3
which complement results in generation of membrane attack complex
C9 (in the final common pathway)
what is the role of CCR7. what are its ligands
directs dendritic cells to lymph nodes
ligands are CCL19 and CCL21
Chemokine ligand 19
what B cells survive tolerance
those that do NOT recognise themselves in bone marrow
what are the components of the adaptive immune system
humoral immunity - B lymphocytes, antibodies
cellular immunity - T lymphocytes (CD4, CD8)
soluble components - cytokines, chemokines
which immunoglobulins are monomers
IgG
IgD
IgE
